Why you need to understand fat solubility to heal your gut

Let’s be honest, you’re not here for a science lesson.  You’re here to improve your gut health, eliminate IBS symptoms like constipation or diarrhea, or reduce the inflammation associated with IBD.  So why does it matter if you know the difference between water soluble and fat soluble?  Simply put…it helps you understand everything else.

As the names suggest, fat soluble molecules dissolve in fat and water soluble molecules dissolve in water.  These molecules can include nutrients, toxins, and pharmaceutical drugs or supplements.  For the most part, it’s the fat soluble toxins and nutrients that become problematic in human health.

Fat soluble vs water solubleImage result for fat soluble membrane

Water soluble nutrients dissolve in water and have specific transporters/channels that bring them in to cells and the circulation.  These transporters are highly specific to nutrients so water soluble toxins tend to stay out of cells.  Since feces, sweat, and urine are water based fluids, water soluble molecules can be excreted pretty easily.

The drawback is that water soluble nutrients need to be eaten regularly because you don’t store much.  Take a large dose of riboflavin and watch your pee turn bright green in an hour or less.  That’s the excess getting dumped in your urine.

Fat soluble molecules, though, can be problematic.  Since cell membranes are also made up of fat, fat soluble molecules can pass through cell membranes, as seen above.

To get a fat soluble molecule out of a cell, it must be made water soluble and removed.  However, you want it going in the proper direction, so it needs to get modified and transported out.  This is where “detoxification” comes in.

Fat soluble molecules also get stored in fat cells, so they can accumulate and cause toxicity.  In fact, when you start losing fat, you release fat soluble toxins stored in your fat cells in to the circulation.

This may sound a little cooky, but if you find a site that says this is junk science I recommend taking what that author says with a grain of salt.  There’s plenty of evidence of this effect that you can check out here(1, 2).  The basic rundown of the second study is:

  • Researchers measured levels of fat soluble pesticides in obese people
  • Obese people had a higher total of stored pesticides and greater levels of detox gene expression in fat tissue
  • When these people lost weight their serum levels of these pesticides increased
  • Over time their total body burden dropped by 15%

There is a chance that they were somehow exposed to more pesticides during weight loss.  But that is extremely unlikely given that they were exposed to less food.  The stored and released theory also jibes well with how fat soluble toxins are handled by the body.

The 3 phases of “detoxification”

Cells have a unique way of dealing with fat soluble molecules called biotransformation.  Biotransformation has 3 phases and is otherwise known as cellular detoxification.  The 3 phases of detoxification are:

  1. Oxidation/reduction/hydrolysis-The fat soluble molecule is made more polar(water soluble).  It also tends to become less toxic, but it sometimes becomes more toxic.
  2. Conjugation-The molecule gets conjugated with one of many different substances to make it fully water soluble.
  3. Transport-The product of conjugation gets transported to the plasma membrane and ejected out of the cell.

Terminology for this process was hijacked by the functional medicine crowd and used to refer to total body detoxification.

Image result for 3 phases of detoxification

It’s not incorrect, per se, to use the 3 phases in this way.  It’s just important to note that this process is not just detoxification.  Many fat soluble molecules, both exogenous and endogenous, go through this process.  In fact, steroid hormones that you produce get altered in the same way.  The same process also metabolizes pharmaceutical drugs.

This is the way fat soluble molecules get processed.  Whether you’re looking at a steroid hormone you produce, a pharmaceutical drug that you take, or a toxin that you somehow ingest.  Of course, this depends on which type of cell we’re talking about.  Cells in the adrenal gland biotransform steroid molecules.  Cells in the liver and gut transform steroid hormones, toxins, and pharmaceutical drug.

Biotransformation in the gut

Before looking in the gut, we have to define some terms…

  • Lumen-In a tubelike structure like the gut, the lumen is the hollow area that things flow through.
  • Enterocyte-Individual cell that forms the intestinal wall
  • Apical surface-The surface of the enterocyte facing the lumen
  • Basolateral surface-The surface of the enterocyte facing inside the body/the bloodstream

Image result for enterocyte apical basolateral

The contents of the digestive tract are mostly water soluble save for the fats you ingest.  On the other side of the enterocyte is the bloodstream, which is also water soluble.  The enterocyte forms a barrier for all molecules, but fat soluble molecules can enter cells because the cell membrane of the enterocyte is made of fat.

Water soluble molecules use transporters and channels to enter the cell on the apical side and leave the cell via transporters and channels on the basolateral side.  Fat soluble molecules enter the cytoplasm of the enterocyte which is water-based.  Inside the cytoplasm of the cell, xenobiotic receptors bind fat soluble molecules and induce the 3 phases of biotransformation.

On both sides of the figure above, you’ll see a bunch of acronyms of differing colors.  Each one of them represents a different cell transporter.  Notice how some located on the apical side transport back in to the lumen.  These transporters are responsible for phase 3 transport, and after a fat soluble molecule gets oxidized and conjugated, it’s spit back in to the lumen for elimination in the feces.

This is the ideal situation, you don’t want these molecules entering the blood circulation.  This is why binding to xenobiotic receptors also downregulates inflammation and upregulates tight junction protein synthesis.  You want that tube known as your gut sealed up as tight as possible when you’re dumping “detoxified” molecules back in to it.  Otherwise they’ll just enter the bloodstream and wreak havoc.

Unfortunately, sometimes things don’t go as planned and some molecules get pumped out the basolateral side and into the blood.  Fortunately, they enter the portal vein and go directly to the liver.  There, they’ll undergo the 3 phases again and either get dumped in to the gut via the bile or circulate to the kidneys where they pass in the urine.

Image result for enterohepatic circulation

The enterohepatic circulation

This process is clever and is referred to as the enterohepatic circulation.  Many things take part in the enterohepatic circulation.  This loop can almost guarantee that most toxins get taken care of.  It’s also valuable for the processing of pharmaceutical drugs, which would accumulate to dangerous levels without it.

A great example of this is the antibiotic Xifaxan, used to treat IBS.  Xifaxan is fat soluble and a powerful inducer of the 3 phases of biotransformation, that’s why it remains in the intestine.  When it binds to something called the pregnane x receptor(PXR) in cells, it puts the 3 phases of detoxification in to overdrive.  Phase 1 & 2 turn it water soluble and spit it right back in to the gut.  Little, if any, enters the general circulation.

During this time, it puts the brakes on inflammation and seals the gut up tight as can be.  This effect may provide more symptomatic relief than the antibiotic effect.  The problem is, it also explains why Xifaxan doesn’t work well for methane predominant small intestinal bacterial overgrowth(SIBO).

Bile enters the picture

Up to this point you’ve got the idea that fat soluble molecules just enter the digestive tract and freely enter cells.  This isn’t quite how it works.  Most of the fats and fat soluble molecules that enter your gut are not in molecular form.  Since the contents in the gut are water soluble, fat doesn’t mix well and forms giant globules.  These globules need to be made smaller so that fat digesting enzymes(lipases) can get to them…Enter bile.

Image result for bile fat emulsification

Bile works by breaking large fat globules up in to tiny emulsion droplets.  This exposes more of the fat to fat digesting enzymes.  Once the emulsion droplets are small enough, they get incorporated in to micelles that carry fat and fat soluble vitamins, drugs and toxins to the cell membrane where they can enter the cell.

Poor fat absorption and fat soluble vitamin status are common in people with bowel disorders.  This is often attributed to low bile output or poor bile activity.  Unfortunately, Xifaxan is fat soluble.  Without adequate bile, it doesn’t enter enterocytes so it doesn’t bind to the pregnane x receptor(3).  This means it doesn’t induce the 3 phases of biotransformation.  It also reduces the antibiotic effect.

Current clinical observations show that Xifaxan isn’t effective for methane predominant SIBO.  This likely has to do with a malfunction in bile production.  Bile acids inhibit the growth of bacteria that generate methane, also called methanogens(4, 5).  It also explains why taking Xifaxan with guar gum improves the effect(6).  Guar gum is also an emulsifier.

Bile acids reduce bacteria in the small intestine, cause the release of antimicrobial peptides in the ileum, and inhibit methane production.  If methanogens are growing in your small intestine, you aren’t producing enough bile.  You’re also probably deficient in fat soluble vitamins as well.

If you can get bile production rolling, you should be able to get a pretty good effect out of Xifaxan whether you have methane- or hydrogen-dominant SIBO*.  The additive effect of Xifaxan with the antimicrobial effects of bile acids provides a perfect 1-2 punch.   Unfortunately, most people aren’t addressing this issue because they don’t know it’s an issue.  This is one of many instances where understanding the difference between water and fat solubility can guide better interventions.

Image result for fat soluble joke


Understanding the difference between water and fat solubility is useful in treating digestive disorders such as SIBO, IBS, and IBD.  It’s also pretty useful in understanding what “detoxification”actually is.  Understanding the process of biotransformation and the receptors and enzymes involved in it can have a major impact on improving your gut health.  In future blogs we’ll look at all this stuff and how we can manipulate things like bile production and biotransformation to our advantage.

*I haven’t gone over increasing bile production because it’s not necessarily a good thing to do without doing other things first.  For example, bacteria in your gut transform water soluble primary bile acids in to fat soluble secondary bile acids, which are toxic to your cells.  More primary bile acids means more potential for secondary bile acids.  I’ll probably cover this soon and dump it in to a blog exclusive to facebook members, who can request to join here.


4 thoughts on “Why you need to understand fat solubility to heal your gut

  1. Samuel Edelman says:

    You write that bile acid keeps methanogenic bacteria from overgrowing in the gut. Is there a similar defense system that keeps hydrogen bacteria from overgrowing? I ask this because I have been battling Hydrogen dominant SIBO for a while which has reoccured, so I am trying to figure out which defense system could be out of whack in my body.

    • cincodm says:

      Hey Samuel, bile acids help control the growth of many different types of bacteria as they are antimicrobial. The problem is,many hydrogen producers are bile tolerant. Many believe that poor motility is to blame for a large proportion of SIBO cases. The primary cause of yours is anybody’s guess.

      I normally point people towards getting their lifestyle dialed in with circadian rhythms, diet, meal frequency, and things of that nature to see where they’re at. From there, if pharmaceutical or supplemental assistance is needed you can make an accurate assessment.

      Hope that helps!

      • Samuel Edelman says:

        I think I might have identified the cause of my SIBO as I have been diagnosed with low elastase (EPI). I guess that a lack of enzymatic action in the small intestine would allow for the wrong type of microbes to proliferate and cause an overgrowth (SIBO)?

        Thanks! After reading your blogs about the importance of circadian rhythm I am trying to focus on getting good sleep and such. Don´t think it is enough to clear my case though and will probably need a herbal therapy to clear the SIBO.

        Appreciate the response!

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